Many types of animals exhibit profound changes in their behavior and physiology at different times of year. In many cases, these changes are triggered by seasonal changes in the length of the day (photoperiod). The duration of nocturnal secretion of melatonin by the pineal gland is also modified by seasonal changes in duration of the photoperiod. In summer, when nights are short, the duration of nocturnal melatonin secretion is correspondingly short. In winter, it is long. In many animals, changes in the duration of nocturnal melatonin secretion chemically mediate the effects of seasonal changes in photoperiod on behavior. Parts of the brain that control seasonal behaviors respond to the melatonin signal via melatonin receptors that detect its presence and interval timing mechanisms that measure the duration of its presence. Our recent research (Z01 MH 02424-02 CPB) has shown that humans, in the course of their evolution, have conserved brain mechanisms similar to those that exist in animals that enable them to detect seasonal changes in daylength and modify the duration of nocturnal melatonin secretion. Human responses to change in photoperiod were detected in experimental conditions in which individuals were exposed to long and short artificial 'days'. In a subsequent experiment (Z01 MH 02424-02 CPB) we investigated whether healthy individuals living in a modern, urban environment (metro Washington, DC area), in which they are routinely exposed to artificial light, are still able to detect seasonal changes in the duration of the night and to respond to these changes by modifying the duration of the nocturnbal period of melatonin secretion. We found that patterns of nocturnal melatonin secretion responded to seasonal changes in the duration of the night, while those in men did not. This finding suggests that there may be gender differences in reponsiveness to artificial light of mechanisms that track seasonal changes in the length of the night. Because of the importance of the duration of nocturnal melatonin secretion as a tranducer of the effects of seasonal changes in the length of the night on animal behavior, it would be important to investigate whether melatonin plays a role in the pathogenesis of seasonal affective disorder (SAD) with recurrent winter depression. Accordingly, in this project, we are assessing whether or not the duration of nocturnal melatonin secretion varies on a seasonal basis in individuals with SAD, as it does in healthy women. If it does, then it might play a role as a chemical transducer of the effects of season on mood in such patients. If it does not, then its failure to respond to season might contribute in some way to the pathogenesis of the disorder. Preliminary results from this project suggest that melatonin is abnormally unresponsive to change of season in patients with SAD.